dAMP | 137793-28-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: dAMP
• 英文别名: [(2R,3S,5R)-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methyl hydrogen phosphate
• CAS: 137793-28-3
• 化学式: C₁₀H₁₃N₅O₆P
• 分子量: 330.217
• InChiKey: KHWCHTKSEGGWEX-RRKCRQDMSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  169
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  dAMP 在 2,2'-二硫二吡啶 、 magnesium sulfate 、 三苯基膦 、 manganese(ll) chloride 作用下， 以 formamide 、 二甲基亚砜 为溶剂， 反应 18.0h， 生成 2'-deoxy NAD+ (sodium salt)
  参考文献：
  名称：

  Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists

  摘要：

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.

  DOI：

  10.1021/jm401497a
• 作为产物：
  描述：

  在 Human histidine triad nucleotide-binding protein 2 作用下， 以 水 为溶剂， 生成 色胺 、 dAMP
  参考文献：
  名称：

  组氨酸三联体核苷酸结合蛋白 HINT1 和 HINT2 具有相似的底物特异性和对信号二核苷酸 Ap4A 的小亲和力

  摘要：

  人类组氨酸三联体核苷酸结合蛋白 2 (hHINT2) 是人类线粒体生物能量学的重要参与者，但对其催化能力或其类似于胞质同工酶 hHINT1 的核苷酸氨基磷酸酯前药 (proTide) 激活活性知之甚少。在这里，发现 hHINT2 的模型氨基磷酸酯底物具有类似的底物特异性特征 (kcat/Km)，但与 hHINT1 相比，kcat 和 Km 值更高。为 hHINT2 确定了更大的最大催化活性 pH 范围（pK1 = 6.76 ± 0.16，pK2 = 8.41 ± 0.07）。此外，通过等温滴定量热法发现已知的 hHINT1-小眼炎诱导转录因子调节分子 Ap4A 与 HINT1 和 HINT2 均未检测到结合。这些结果表明，尽管它们的序列和定位存在差异，

  DOI：

  10.1002/1873-3468.13745

文献信息

• Gas Phase Reactions of Trimethylborate with the [M − H]− Ions of Nucleotides and Their Non-Covalent Homo- and Heterodimer Complexes
  作者：Ana K. Vrkic、Richard A. J. O'Hair

  DOI：10.1071/ch02183

  日期：——

  heterodimers. In addition, the collision-induced dissociation (CID) reactions of the [(dXMP)n − H]– (n = 1 or 2) as well as the [dXMP + dYMP – H + (CH3O)3B – 3(CH3OH)]– ions (where nucleotides X, Y = A, C, G, or T) were studied. The latter fragment to form [dXMP – H + BPO4]– and [dXMP – 3H + BPO3]– ions (where X = A, C, G, or T), while [dXMP – H]– ions fragment by neutral base loss. The homo- and heterodimers

  硼酸三甲酯 (TMB) 与核苷酸的去质子化单体、同源和异源二聚体离子（2'-deoxyadenosine-5'-monophosphate [dAMP]、2'-deoxycytidine-5'-monophosphate [dCMP]、2'-deoxyguanosine-5 '-单磷酸盐 [dGMP] 和 2'-脱氧胸苷-5'-单磷酸盐 [dTMP]）在四极离子阱质谱仪中通过添加同时消除一个或两个甲醇分子（单体）、一个或三个甲醇分子（同二聚体） ) 和三个甲醇分子（异二聚体）。反应模式似乎会影响观察到的速率，只有一个甲醇分子的损失对应于最快的速率。单体似乎存在结构-反应性相关性，[dGMP – H]– 离子（采用鸟嘌呤部分的顺式构象）通过仅损失一个甲醇分子与 TMB 反应最快。对于同二聚体和异二聚体，没有观察到这样的结构反应趋势。此外，[(dXMP)n - H]– (n = 1 或 2) 以及
• The strength of the template effect attracting nucleotides to naked DNA
  作者：E. Kervio、B. Claasen、U. E. Steiner、C. Richert

  DOI：10.1093/nar/gku314

  日期：2014.6.17

  neighboring strand. Combined with rate constants for the chemical step of extension and hydrolytic inactivation, our quantitative theory explains why some enzyme-free copying reactions are incomplete while others are not. For example, for GMP binding to ribonucleic acid, inhibition is a significant factor in low-yielding reactions, whereas for amino-terminal DNA hydrolysis of monomers is critical. Our results

  遗传信息的传递依赖于模板-引物复合物中核苷磷酸和模板碱基之间的沃森-克里克碱基配对。无酶引物延伸是最纯粹的传输过程形式，没有聚合酶的任何伴侣效应。这种简单的序列复制形式与生命起源密切相关，并为阅读遗传信息提供了新的机会。在这里，我们报告了（脱氧）核苷酸和模板-引物复合物之间复合物的解离常数，由核磁共振和未活化核苷酸对无酶引物延伸的抑制作用确定。根据序列上下文，K d的范围从胸苷单磷酸结合发夹末端腺嘌呤的 280 mM 到与相邻链的序列内部的脱氧鸟苷单磷酸结合的 2 mM。结合延伸和水解失活的化学步骤的速率常数，我们的定量理论解释了为什么一些无酶复制反应不完整，而另一些则不完整。例如，对于 GMP 与核糖核酸的结合，抑制是低产反应的一个重要因素，而单体的氨基末端 DNA 水解则至关重要。因此，我们的结果为无酶复制提供了定量基础。
• Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists
  作者：Christelle Moreau、Tanja Kirchberger、Joanna M. Swarbrick、Stephen J. Bartlett、Ralf Fliegert、Timur Yorgan、Andreas Bauche、Angelika Harneit、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm401497a

  日期：2013.12.27

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.
• Histidine triad nucleotide‐binding proteins HINT1 and HINT2 share similar substrate specificities and little affinity for the signaling dinucleotide Ap4A
  作者：Alexander Strom、Cher Ling Tong、Carston R. Wagner

  DOI：10.1002/1873-3468.13745

  日期：2020.5

  Human histidine triad nucleotide‐binding protein 2 (hHINT2) is an important player in human mitochondrial bioenergetics, but little is known about its catalytic capabilities or its nucleotide phosphoramidate prodrug (proTide)‐activating activity akin to the cytosolic isozyme hHINT1. Here, a similar substrate specificity profile (kcat/Km) for model phosphoramidate substrates was found for hHINT2 but

  人类组氨酸三联体核苷酸结合蛋白 2 (hHINT2) 是人类线粒体生物能量学的重要参与者，但对其催化能力或其类似于胞质同工酶 hHINT1 的核苷酸氨基磷酸酯前药 (proTide) 激活活性知之甚少。在这里，发现 hHINT2 的模型氨基磷酸酯底物具有类似的底物特异性特征 (kcat/Km)，但与 hHINT1 相比，kcat 和 Km 值更高。为 hHINT2 确定了更大的最大催化活性 pH 范围（pK1 = 6.76 ± 0.16，pK2 = 8.41 ± 0.07）。此外，通过等温滴定量热法发现已知的 hHINT1-小眼炎诱导转录因子调节分子 Ap4A 与 HINT1 和 HINT2 均未检测到结合。这些结果表明，尽管它们的序列和定位存在差异，